The polymorphonuclear leukocyte (PMN) is found in large concentrations within inflammed corneas. The historlogic damage noted in such corneas, particularly following bacterial infection, has often been ascribed to the infecting microbial agent or it products. However, recent reports suggest the PMN itself may play an important role in damaging the cornea. In the proposed project we intend to define the role of the PMN in the production of norneal damage. The proposed studies will determine the relative importance of each of the routes through which PMNs enter inflammed corneas (tear film, limbal vessels, anterior chamber) and which microbial or host-derived substances attract PMNs into coraneas. They will also determine whether the PMN itself or its enzymatic and metabolic by-products can induce corneal damage, and whether such damage can be imnimized through the use of various inhibitors of PMN adherence and chemotaxis or by the inhibition of production or activity of toxic PMN by products in corneas. We will also assess the importance of differences in the function and metabolism of rabbit and guinea pig PMNs as an explanation for the differences noted previously in experimental keratitis between these two species. This should allow determination of which animal species serves as the better model for human PMN mediated corneal disease. Major methodologies to be employed in this project include quantitative assessment of intracorneal inflammation by in vivo flash labelling of PMNs with tritiated thymidine or throuigh transsfusion of radiolabelled PMNs. Ingress of radiolabelled PMNs will be quantitated by measurement of corneal radioactivity. The ability of various agents when administred systemically or topically to decrease ingaress of PMNs into corneas or to inhibit PMN enzymatic or metabolic activity will be evaluated by these techniqes as well as by histologic, autoradiographic and electron microscopic means. The imporatnce of these studies lies in the fact that the therapy of human keratitis is presently aimed primarily at eradication of invading microbial agents. The proposed studies will help define the role of the PMN in the mediation of corneal damage in inflammatory disease of the cornea and methods through which such damage may be minimized